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Titolo:
CA-45 ACCUMULATION IN RAT-BRAIN AFTER CLOSED-HEAD INJURY - ATTENUATION BY THE NOVEL NEUROPROTECTIVE AGENT HU-211
Autore:
NADLER V; BIEGON A; BEITYANNAI E; ADAMCHIK J; SHOHAMI E;
Indirizzi:
PHARMOS LTD,KIRYAT WEIZMANN IL-76326 REHOVOT ISRAEL HEBREW UNIV JERUSALEM,DEPT PHARMACOL JERUSALEM ISRAEL
Titolo Testata:
Brain research
fascicolo: 1-2, volume: 685, anno: 1995,
pagine: 1 - 11
SICI:
0006-8993(1995)685:1-2<1:CAIRAC>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
CALCIUM ACCUMULATION; CEREBRAL-ISCHEMIA; NEURONAL DAMAGE; AMINO-ACIDS; NEUROTOXICITY; RECEPTORS; POTASSIUM; BLOCKADE; TRAUMA;
Keywords:
CALCIUM ACCUMULATION; (45)CALCIUM; CANNABINOID; CLOSED HEAD INJURY; HEAD TRAUMA; HU-211;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
V. Nadler et al., "CA-45 ACCUMULATION IN RAT-BRAIN AFTER CLOSED-HEAD INJURY - ATTENUATION BY THE NOVEL NEUROPROTECTIVE AGENT HU-211", Brain research, 685(1-2), 1995, pp. 1-11

Abstract

Ca-45 accumulation was studied autoradiographically as a marker for lethally injured brain tissue following closed head injury (CHI), and applied to an investigation of the neuroprotective effect of the non-psychoactive cannabinoid(+)-(3S,4S)-7-hydroxy-D-6 tetrahydro-cannabinol 1,1-dimethylheptyl (HU-211). Amassment of Ca-45 in rat brain was examined 24 or 72 h after induction of CHI in the left hemisphere by a weight-drop device. Concentration of Ca-45 within 15 different brain regions was assessed by relative optical density. There was increased Ca-45accumulation in the hemisphere ipsilateral to the side of the insult as compared with the contralateral hemisphere. The highest density of radioactive labeling was found in the anterior cortex and in the frontal parts of the parietal cortex, with accumulation expanding as a function of time post injury. On the third day following trauma the amountof accumulated Ca-45 was higher than that at 24 h after CHI, with more distant Ca-45-accumulating structures involved: the ventral posterolateral nucleus of the thalamus and the substantia nigra. Histological examination revealed necrotic tissue in the regions accumulating Ca-45. HU-211, a stereoselective inhibitor of the N-methyl-D-aspartate (NMDA) receptor, was injected immediately after induction of trauma. One day after trauma, HU-211 had significantly decreased both the volume ofthe Ca-45 accumulating zone and the concentration of the amassed radioisotope. In the HU-211 treated rats a considerable reduction in radioactive labeling was also found 72 h after trauma. The ability of HU-211 to decrease Ca-45 accumulation after head trauma is probably due to its ability to attenuate Ca2+ fluxes through the NMDA receptor-mediated calcium channels and to reduce the depolarization evoked Ca2+ fluxes. On the basis of our results, HU-211 seems to be a promising therapeutic agent for head trauma in humans.

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Documento generato il 12/07/20 alle ore 09:01:04